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What's next? Rescue protocols for canine lymphoma

Lymphoma is the third most-common cancer in dogs and is considered to be very responsive to chemotherapy. With standard CHOP-L protocols (those that include L'asparaginase, vincristine, cyclosphosphamide, doxorubicin and prednisone), reported first-remission rates are 80 percent to 90 percent, with the average first remission between eight and 12 months.

There are several CHOP-L protocols published for use, including the Wisconsin-Madison protocol, AMC protocol and VELCAP (Moore 2001). Although there are some differences among them in terms of scheduling, dosages and addition of other chemotherapeutics, the differences are minor and the protocols are considered to be equally effective.

There is some debate as to whether treatment should include a maintenance phase, lasting one to three years, or whether treatment should be discontinued sooner. The trend has been to use shorter-term protocols (12 to 24 weeks), with the theory that the development of drug resistance may be delayed as lymphoma cells are not continuously being exposed to chemotherapy.

Short-term protocols have the advantages of being less expensive, requiring fewer visits and potentially having fewer side effects.

When deciding on what protocol to use for initial treatment, it is important to take into account prognostic factors, including anatomic location, stage, grade, substage, immunophenotype and presence of hypercalcemia or a mediastinal mass.

Most "average" dogs (Stage II-IVa B-cell intermediate to high-grade lymphoma) will benefit from a CHOP-L type of protocol.

It has not been documented whether dogs with negative prognostic factors (i.e., substage b) will have the same remission duration with a short-term protocol compared to "average" dogs with lymphoma. These dogs may be more effectively treated with protocols that include a maintenance phase.

Those with T-cell lymphoma or certain anatomic locations (cutaneous or gastrointestinal) may benefit from the use of protocols such as MOPP as a first-line treatment.

First remissions tend to be easier to achieve and treatment protocols are more standardized. Subsequent remissions can be more difficult to achieve as well as being shorter in duration. Most rescue protocols will have response rates of around 30 percent to 50 percent, with a duration of 60 to100 days. There are fewer "rules" that influence the selection of rescue protocols compared to the initial protocol.

When selecting a rescue protocol, factors that need to be taken into account include what drugs were used initially, how long the first remission was, what toxicity was seen during the first remission, owner expectations and the overall clinical status of the patient.

In general, the risk of side effects is similar although chronic myelosuppression, particularly thrombocytopenia, can be seen with dogs that are heavily pre-treated. This may necessitate dose reductions, treatment delays or cessation of treatment.

The length of treatment with a rescue protocol is not standard. In our clinic, most rescue protocols are administered for no less than six months but no more than a year, providing that the patient continues to respond.

Drug resistance

It is important to understand some principles of drug resistance in order to rationally select a rescue protocol (Ogilvie, 1995). Drug resistance is responsible for the failure of chemotherapy in those cancers that initially are considered to be "chemoresponsive." Resistance can either be de novo (present prior to any treatment) or acquired.

Table 1. Mechanisms of drug resistance

There are multiple mechanisms that can convey drug resistance and, for many drugs, there is more than one mechanism that can induce resistance (Table 1).